Abstract 5096: SDF-1/CXCR4 Gene Polymorphisms are Associated with Blood SDF-1α Proteins and Endothelial Progenitor Cells in Bruneck Population
Background: The axe of stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) plays a critical role in the progenitor cell homing, mobilization and differentiation. However, no data exists concerning the effect of the SDF-1/CXCR4 gene polymorphisms on protein levels and endothelial progenitor cells (EPCs) in blood. The aim of this study was to examine the potential associations between SDF-1/CXCR4 gene polymorphisms and the levels of blood SDF-1α and EPC number and the predictive value for SDF-1α for the EPC numbers.
Methods and Results: In the population-based Bruneck Study, serum SDF-1α levels (2000’s and 2005’s), five SDF-1 gene polymorphisms (rs2297630, rs266085, rs266087, rs1801157, rs1413519), and two CXCR4 gene polymorphisms (rs16832740, rs16832740) were assessed as part of the fourth follow-up evaluation (2005) in 571 subjects. EPCs from all of 571 subjects were cultured using two techniques, i.e. adhesion and colony-formation methods. Serum SDF-1α level increased with age (r=0.270, p<0.001) and was higher in women (2619 vs. 2497, p=0.002). In a step forward multivariate linear regression analysis serum SDF-1α level was independently related with alcohol consumption, MMP-9, hsCRP, cystatin C, fibrinogen, reticulocytes and homocytein. Moreover, serum SDF-1α levels were significantly and inversely related to EPC number (p<0.001) in the 2005 cross-sectional evaluation. Importantly, 2000s’ serum SDF-1α levels were prospective associated with 2005s’ EPC number (p=0.009). Finally, one SDF-1 gene polymorphism (rs2297630), but not other SDF-1 and CXCR4 gene polymorphisms, was significantly associated with EPC number (p=0.002) and serum SDF-1α level (p=0.001). The homozygous mutation (AA), but not heterozygous mutation (GA) and wild-type homozygotes (GG), were associated with significantly lower EPC number and higher levels of serum SDF-1α, respectively.
Conclusions: Our data indicate that SDF-1 gene polymorphism (rs2297630) determine SDF-1α level and circulating EPC number, and that serum SDF-1α level can predict EPC number in the peripheral blood, implying an impact of SDF-1 SNP in the SDF-1α gene transcription.